Anamorelin is used to treat cachexia in patients with various malignant tumors, including non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer.

Anamorelin instruction manual

Product Name: LuciAnam

Manufacturer: Lucius Pharmaceuticals

Chinese name: Anamorelin

English Name: Anamorelin

Drug approval number: 02 L 1063/24

 

 

【Summary】

Anamorelin acts on the ghrelin receptor GHS-R1a (growth hormone-releasing factor receptor type 1a). The drug promotes the secretion of growth hormone (GH) by activating GHS-R1a and stimulating appetite, thereby increasing body weight.

The drug binds to recombinant human GHS-R1a and acts on rat pituitary cells to promote GH secretion (in vitro). This drug increases plasma GH concentrations in rats after a single oral administration. After repeated oral administration to rats, the drug increases food intake and body weight.

 

【Indications】

For the treatment of cachectic patients with unresectable advanced, recurrent non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer

It can be used for cancer cachexia patients who have not responded well to nutritional therapy, have lost more than 5% of their body weight within 3.6 months, have loss of appetite, and meet more than 2 of the following ①-③:

① Fatigue or tiredness

② Decreased musculoskeletal function

③CRP value exceeds 0.5mg/dl, hemoglobin value is less than 12g/dl or albumin value is less than 3.2g/dl

 

【Specification】

50mg/tablet, 100 tablets/bottle.

 

【Storage】

Store at 20°C to 25°C (68°C to 77°F); short-distance transport is permitted at a temperature range of 15 to 30°C (59–86°F).

 

【Usage and Dosage】

Adults take 100 mg orally once a day on an empty stomach (1 hour before or 2 hours after a meal)

 

【Main side effects】

Increased γ-GTP (serum γ-glutamyl transpeptidase) and glycosylated hemoglobin.

【Adverse Reactions】

Serious adverse reactions:

1. Inhibition of the stimulus conduction system, abnormal electrocardiogram (obvious prolongation of the PR interval or QRS width, QT prolongation, etc.), sometimes atrioventricular block, tachycardia, bradycardia, palpitations, decreased blood pressure, superoventricular extrasystoles, etc.

2. If high blood sugar or diabetes worsens, you should pay attention to symptoms such as thirst and frequent urination.

3. Liver dysfunction, which is sometimes accompanied by an increase in AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), γ-GTP (serum γ-glutamyl transpeptidase), blood bilirubin, etc.

 

【Taboo】

1. Patients with a history of allergy to the ingredients of this drug

2. Patients with congestive heart failure [heart function is suppressed and symptoms may worsen]

3. Patients with myocardial infarction or angina pectoris [heart function is suppressed and symptoms may worsen]

4. Patients with severe stimulation conduction system disorders (complete atrioventricular block, etc.) [This drug has a sodium channel inhibitory effect, which inhibits the stimulation conduction system and may worsen the condition]

5. Patients who are taking any of the following drugs: clarithromycin, inavir, itraconazole, nelfonavir, Morinda officinalis, boriconazole, indigomycin, nelfinavir, sakinavir, tiploprvir, ritonavir-containing preparations, and convitastat-containing preparations. Patients who have difficulty taking food orally due to organic abnormalities of the digestive tract such as digestive tract occlusion.

6. Patients with moderate or above liver dysfunction (Child-Pugh classification B and C) [Since the liver mainly helps this drug to disappear from the body, the blood drug concentration increases and the stimulus conduction system may be inhibited.]

 

【Notes】

1. This drug has a sodium channel inhibitory effect, so it has an inhibitory effect on the stimulus conduction system. Since ECG abnormalities (obvious PR interval or QRS width extension, QT interval extension, etc.) will occur during administration, ECG, pulse, blood pressure, cardiothoracic ratio, electrolytes, etc. should be measured regularly before and during administration. If abnormalities are found, administration should be stopped. In addition, special attention should be paid in the early stage of administration.

2. Since hyperglycemia may occur sometimes, blood sugar and urine sugar should be measured regularly before and during the administration of this drug.

3. Since liver dysfunction may occur sometimes, liver function tests should be performed regularly before and during the administration of this drug. Generally speaking, the physiological functions (renal function, liver function, immune function, etc.) of the elderly decline, so it is necessary to observe the patient's condition and take the drug with caution.

4. For pregnant women or women who may become pregnant, the drug should be administered only when it is judged that the benefits of treatment outweigh the risks. By injecting ghrelin or ghrelin-like substances into mice, it was found that embryogenesis was delayed, fetal weight was low, pregnancy rate decreased, and the number of fetuses decreased. In addition, although the placental permeability of this agent is unclear, it is possible to pass through the placenta considering its high fat solubility and weak alkalinity.

5. Considering the efficacy advantage and the nutritional benefits of breast milk, breastfeeding women need to decide whether to continue breastfeeding. (The transfer of this agent into breast milk is not clear, but considering its high fat solubility and weak alkalinity, it is possible to transfer into breast milk)

 

Safety and efficacy

Anamorelin is the first drug to treat cancer cachexia. Clinical data show that Anamorelin has the effect of increasing weight, muscle mass and appetite in cancer cachexia patients. The launch of Anamorelin will provide a new treatment option for cancer cachexia patients in Japan who have no treatment options, and help improve the quality of life of such patients.

Two randomized, double-blind, placebo-controlled studies (ROMANA 1 and ROMANA 2) of Anamorelin for the treatment of patients with non-small cell lung cancer (NSCLC) published in The Lancet in 2016 showed that the median weight gain in the placebo group in the two trials was –0.47kg and –0.98kg, respectively. The weight of patients in the ROMANA 1 and ROMANA 2 treatment groups increased compared with the placebo group, with a median weight gain of 0.99kg and 0.65kg, respectively.

This global study found that Anamorelin increased muscle mass in patients with advanced NSCLC cachexia, but failed to improve grip strength. There was no statistical difference in the incidence of grade 3-4 treatment-related adverse events between the treatment groups in the two clinical trials. The most common grade 3-4 adverse event was hyperglycemia. Considering safety and efficacy, Anamorelin can be used as a treatment option for patients with cancer cachexia.

Anamorelin was approved in Japan in January 2021. The approval was based primarily on the results of two clinical studies in patients with cancer cachexia in Japan: 1) a multicenter, placebo-controlled, randomized, double-blind, parallel-group study in patients with non-small cell lung cancer (NSCLC) (ONO-7643-04 study); and 2) a multicenter, open-label, non-controlled Phase III study in patients with colorectal cancer, gastric cancer, and pancreatic cancer (ONO-7643-05 study). In these studies, Anamorelin showed effects on increasing body weight, muscle mass, and appetite in patients with cachexia in cancer patients.